do Amaral Stéphanie R, Amantino Camila F, Atanasov Aleksandar, Sousa Stefanie Oliveira, Moakes Richard, Oliani Sonia Maria, Grover Liam M, Primo Fernando L
Department of Bioprocess and Biotechnology Engineering, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, Brazil.
São Paulo Federal Institute of Education, Science and Technology (IFSP), Matão 15991-502, SP, Brazil.
Pharmaceuticals (Basel). 2024 Sep 4;17(9):1169. doi: 10.3390/ph17091169.
Skin inflammation associated with chronic diseases involves a direct role of keratinocytes in its immunopathogenesis, triggering a cascade of immune responses. Despite this, highly targeted treatments remain elusive, highlighting the need for more specific therapeutic strategies. In this study, nanocapsules containing quinizarin (QZ/NC) were developed and evaluated in an in vitro model of keratinocyte-mediated inflammation, incorporating the action of photodynamic therapy (PDT) and analyzing permeation in a 3D skin model. Comprehensive physicochemical, stability, cytotoxicity, and permeation analyses of the nanomaterials were conducted. The nanocapsules demonstrated desirable physicochemical properties, remained stable throughout the analysis period, and exhibited no spectroscopic alterations. Cytotoxicity tests revealed no toxicity at the lowest concentrations of QZ/NC. Permeation and cellular uptake studies confirmed QZ/NC permeation in 3D skin models, along with intracellular incorporation and internalization of the drug, thereby enhancing its efficacy in drug delivery. The developed model for inducing the inflammatory process in vitro yielded promising results, particularly when the synthesized nanomaterial was combined with PDT, showing a reduction in cytokine levels. These findings suggest a potential new therapeutic approach for treating inflammatory skin diseases.
与慢性疾病相关的皮肤炎症在其免疫发病机制中涉及角质形成细胞的直接作用,引发一系列免疫反应。尽管如此,高度靶向的治疗方法仍然难以实现,这凸显了更具特异性治疗策略的必要性。在本研究中,开发了含有醌茜(QZ/NC)的纳米胶囊,并在角质形成细胞介导的炎症体外模型中进行评估,结合光动力疗法(PDT)的作用并分析其在三维皮肤模型中的渗透情况。对纳米材料进行了全面的物理化学、稳定性、细胞毒性和渗透分析。纳米胶囊表现出理想的物理化学性质,在整个分析期间保持稳定,且未出现光谱变化。细胞毒性测试表明,在最低浓度的QZ/NC下没有毒性。渗透和细胞摄取研究证实了QZ/NC在三维皮肤模型中的渗透,以及药物在细胞内的掺入和内化,从而提高了其药物递送效果。所建立的体外诱导炎症过程的模型产生了有前景的结果,特别是当合成的纳米材料与PDT联合使用时,细胞因子水平有所降低。这些发现提示了一种治疗炎症性皮肤病的潜在新治疗方法。